Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques
Victoria E. Walker-Sperling, Noe B. Mercado, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Mark G. Lewis, Jeffrey P. Murry, Yunling Yang, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael, Maria Grazia Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. Siliciano, Dan H. Barouch
Abstract
The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.